Abstract: Background　The incidence of gout is steadily rising，which has become a major public health issue.The important role of adenosine triphosphate-binding cassette transporter G2 （ABCG2） in uric acid metabolism has drawn extensive attention and become a research focus in recent years.A study of ABCG2 would therefore be favorable for identifying the molecular biological mechanism of the pathogenesis of gout，so as to provide new approaches for the diagnosis and treatment of gout.Objective　To observe the variation of ABCG2 expression in peripheral blood mononuclear cells （PBMCs） of patients with primary gouty arthritis（GA），and to explore the potential role of ABCG2 in primary GA.Methods　Eighty-two male outpatients and inpatients with primary GA （GA group） were selected from the Department of Rheumatology and Immunology，Affiliated Hospital of North Sichuan Medical College from June 2016 to February 2017，including 41 each with acute GA （AGA subgroup） and intermittent GA （IGA subgroup）．Based on the serum uric acid （SUA） level，the patients were further divided into the group with SUA <420 μmol/L （NUA subgroup，n=31） and the group with SUA≥420 μmol/L（HUA subgroup，n=51）．Primary GA patients were compared to 46 healthy males who received physical examination at the Physical Examination Center of this hospital over the same period （HC group）．The patients were tested for SUA，creatinine，cystatin C （Cys-C），erythrocyte sedimentation rate （ESR），and hypersensitive C-reactive protein （hs-CRP）．RT-qPCR and Western blotting were used to detect the expression of ABCG2 mRNA and protein in PBMCs for all the subjects.Results　The expression of ABCG2 mRNA in PBMCs was higher in GA group than in HC group （P<0.05）．The expression of ABCG2 mRNA and protein in PBMCs was higher in IGA subgroup than in AGA subgroup （P<0.05）；the expression of ABCG2 mRNA and protein in PBMCs was lower in HC group than in IGA subgroup （P<0.05）；there were no significant differences between AGA subgroup and HC group in ABCG2 mRNA or protein expression in PBMCs （P>0.05）．The expression of ABCG2 mRNA and protein in PBMCs was higher in HUA subgroup than in NUA subgroup （P<0.05）；the expression of ABCG2 mRNA and protein in PBMCs was lower in HC group than in HUA subgroup （P<0.05）；there were no significant differences between NUA subgroup and HC group in ABCG2 mRNA or protein expression in PBMCs （P>0.05）．In primary GA patients，the expression of ABCG2 mRNA showed a positive correlation with SUA （r=0.235，P=0.033），a negative correlation with serum creatinine and Cys-C （r=-0.227，-0.229，P=0.044，0.043，respectively），but demonstrated no linear correlation with ESR and hs-CRP （r=-0.181，0.027，P= 0.112，0.824，respectively）．Conclusion　ABCG2 is highly expressed in PBMCs of patients with primary GA，and is involved in uric acid transportation.However，it was not shown to be associated with the  inflammation in primary GA.Expression of ABCG2 in PBMCs is down-regulated in patients with primary GA with renal dysfunction.

Key words: Arthritis, gouty；Uric acid；Adenosine triphosphate-binding cassette transporter G2

摘要： 背景　痛风不断攀升的高发病率已经成为重大的公共健康问题。三磷酸腺苷结合盒转运蛋白G2（ABCG2）在尿酸代谢中的重要作用已经得到广泛关注，成为近年来研究的热点。因此，针对ABCG2的研究有利于发现痛风发病的分子生物学机制，为痛风的诊断、治疗提供新的思路。目的　观察原发性痛风性关节炎患者外周血单个核细胞（PBMCs） ABCG2表达水平的变化情况，探究ABCG2在原发性痛风性关节炎中可能的作用。方法　选取2016年6月—2017年2月于川北医学院附属医院风湿免疫科门诊就诊及住院的男性原发性痛风性关节炎患者（GA组）82例，其中急性期痛风（AGA亚组）和间歇期痛风（IGA亚组）患者各41例。依据患者血尿酸水平进一步分为血尿酸<420 μmol/L痛风亚组（NUA亚组）31例、血尿酸≥420 μmol/L痛风亚组（HUA亚组）51例。另选取同期川北医学院附属医院体检中心的男性健康体检者（HC组）46例。检测患者血尿酸水平、肌酐水平、胱抑素C（Cys-C）水平、红细胞沉降率（ESR）、超敏C反应蛋白（hs-CRP）水平；采用RT-qPCR、Western blotting法分别检测受试者PBMCs ABCG2 mRNA及蛋白表达水平。结果　GA组PBMCs ABCG2 mRNA表达水平高于HC组（P<0.05）。IGA亚组PBMCs ABCG2 mRNA及蛋白表达水平高于AGA亚组（P<0.05）；HC组PBMCs ABCG2 mRNA及蛋白表达水平低于IGA亚组（P<0.05）；AGA亚组与HC组PBMCs ABCG2 mRNA及蛋白表达水平比较，差异无统计学意义（P>0.05）。HUA亚组PBMCs ABCG2 mRNA及蛋白表达水平高于NUA亚组（P<0.05）；HC组PBMCs ABCG2 mRNA及蛋白表达水平低于HUA亚组（P<0.05）；NUA亚组与HC组PBMCs ABCG2 mRNA及蛋白表达水平比较，差异无统计学意义（P>0.05）。男性原发性痛风性关节炎患者ABCG2 mRNA表达水平与血尿酸水平呈正相关（r=0.235，P=0.033），与肌酐水平、Cys-C水平呈负相关（r值分别为-0.227、-0.229，P值分别为0.044和0.043），与ESR、hs-CRP水平无直线相关关系（r值分别为-0.181、0.027，P值分别为0.112、0.824）。结论　ABCG2在原发性痛风性关节炎患者PBMCs中高表达，并参与尿酸的转运，但未发现其与原发性痛风性关节炎的炎症过程相关；且肾功能异常的原发性痛风性关节炎患者的PBMCs ABCG2表达下调。

关键词: 关节炎, 痛风性；尿酸；三磷酸腺苷结合盒转运蛋白G2